Induction of innate immunity and its perturbation by influenza viruses
© The Author(s) 2015. This article is published with open access at Springerlink.com and journal.hep.com.cn
Induction of innate immunity and its perturbation by influenza viruses
Mohsan Ullah Goraya 2 3
Song Wang 2 3
Muhammad Munir 1 2
Ji-Long Chen 0 2 3
0 CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences , Beijing 100101, China Received June 6, 2015 Accepted June 29, 2015
1 The Pirbright Institute , Ash Road, Pirbright, Woking GU24 0NF , UK
2 influenza A virus , innate immunity, immune
3 College of Animal Science, Fujian Agriculture and Forestry University , Fuzhou 350002 , China
Influenza A viruses (IAV) are highly contagious pathogens causing dreadful losses to human and animal, around the globe. IAVs first interact with the host through epithelial cells, and the viral RNA containing a 5′-triphosphate group is thought to be the critical trigger for activation of effective innate immunity via pattern recognition receptors-dependent signaling pathways. These induced immune responses establish the antiviral state of the host for effective suppression of viral replication and enhancing viral clearance. However, IAVs have evolved a variety of mechanisms by which they can invade host cells, circumvent the host immune responses, and use the machineries of host cells to synthesize and transport their own components, which help them to establish a successful infection and replication. In this review, we will highlight the molecular mechanisms of how IAV infection stimulates the host innate immune system and strategies by which IAV evades host responses.
escape
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Influenza A viruses (IAV) cause highly pathogenic
respiratory problems in human and animals. It is the major cause of
annual epidemics and occasional pandemics in humans,
responsible for 3–5 million cases of severe clinical infections
and 250,000 to 500,000 fatal cases every year throughout
the world (Stohr, 2002). Infection with influenza virus varies
from subclinical infection of upper respiratory tract to lethal
infection of lower respiratory system. Due to differences in
pathogenesis of various influenza viruses, biology of the
disease is not fully understood. Influenza virus infection
induces host innate immune responses, which results in the
termination of virus replication. On the other hand, IAV has
evolved multiple strategies to circumvent the host innate
immunity to establish a successful infection and replication.
In addition to typical seasonal infections, IAV can also
undergo substantial changes (recombination/antigenic shift)
that leave imprints of infection with little to no protective
immunity and uplift mortality rate even among healthy young
adults infected with IAV (Horimoto and Kawaoka, 2001;
Palese, 2004). Only, the last century we have observed three
major pandemics: the 1918 Spanish flu, 1957 Asian flu, and
the 1968 Hong Kong flu; with the 1918 pandemic being the
most concerning and significant, causing an estimated
30–50 million deaths worldwide (Horimoto and Kawaoka,
2001, 2005). Furthermore, the recent appearance of IAV
strains with pandemic potential, such as H1N1 “swine flu”
and H5N1 avian influenza, have highlighted the importance
of studies about IAV infections and the innate and adaptive
immune responses that control and eliminate infection.
Thus, this review will focus on discussion of host innate
immune responses to IAV infection and viral escape from the
innate sensing.
BIOLOGY AND STRUCTURE OF IAV
Influenza viruses are categorized in the family of
Orthomyxoviridae. The virus particle is enveloped and
contains a segmented, single-stranded, negative sense RNA
genome (Klenk et al., 2004). Its genome possesses eight
segments encoding 13 proteins (Jagger et al., 2012), out of
which 8 are considered core proteins whereas the rest are
called accessory proteins. Additionally, a putative open
reading frame (ORF) in the positive-sense of segment 8 has
been identified, which encodes for a hypothetical negative
sense protein (NSP) of ∼25 kDa (Zhirnov et al., 2007).
However, the role of NSP still remains elusive. Another
protein encoded within segment 2 (in addition to PB1 and
PB1-F2) has been identified, termed N40 (Wise et al., 2009).
Morphologically, the viral particles are creased with a lipid
bilayer, which is derived from the host plasma membrane.
The lipid bilayer contains almost 500 spikes (each of
10–14 nm), of viral proteins hemagglutinin (HA) and
neuraminidase (NA), protruded out from the envelope. These
spikes appear as either rod-shaped (HA) or mushroom
shaped (NA). The ratio of HA to NA generally varies from 4:1
to 5:1. The high density of HA is probable to enhance the
chances for viral attachment. Additionally, matrix protein 2
(M2) is also enriched into the lipid envelope. The ratio
between M2 and HA is usually about 1:10 to 1:100 (Zebedee
and Lamb, 1988). Envelope viral glycoproteins (HA and NA)
have stumpy kinesis within envelope. These two (...truncated)